斑马鱼在心血管病治疗药物筛选研究中的应用

斑马鱼因体积小、成本低廉、身体透明、基因组与人类高度同源及生理生化特征与哺乳动物相似等特点,近年来广泛应用于人类疾病的基础研究.通过高通量小分子筛选等方法,可在多种斑马鱼模型体内开发心血管疾病的新型治疗药物,鉴定现存药物的靶标或预测特定小分子药物的心血管毒性.     

斑马鱼在血小板研究中的应用

斑马鱼是心血管生理病理研究中常用的模式生物。斑马鱼血小板与人类血小板具有高度相似性,而且斑马鱼具有体外受精、繁殖力强、胚胎透明等优点,越来越多关于血小板的研究利用斑马鱼作为模式生物,并取得了一定的进展。此文简要概述了斑马鱼血小板与人类血小板的相似性,以及利用斑马鱼作为模式生物研究血小板的一些进展。     

全基因组关联分析在消化系肿瘤中的研究进展

全基因组关联分析(genome-wide association study,GWAS)是应用人类基因组中单核苷酸多态性(single nucleotide polymorphism,SNP)为标记进行分析,以期发现影响复杂性疾病发生的遗传特征的一种新策略.因其可在全基因组范围内进行整体研究,能够一次性对疾病与基因的关联进行轮廓性概览,所以在过去的5年中,全基因组关联研究方法已被证明是研究复杂疾病一种有效手段.近年,各国科学家运用全基因组关联分析在人类肿瘤,特别是在消化系肿瘤的研究中取得了一系列重要的研究成果,本文将综述消化系肿瘤GWAS研究进展,并展望GWAS所面临的挑战及可能的解决策略.     

单核苷酸多态性在肾脏病研究中的应用前景

人类基因组是一个稳定的体系 ,同时也是一个变异的体系。基因组结构的稳定性保证了人类作为一个物种的共同性和稳定性 ,基因组序列的可变性形成了不同种族、群体和个体间基因组的多态性。随着人类基因组计划的进展 ,研究基因组中的序列变异即ＤＮＡ多态性成为必然 ,并日益显示出其重要意义。在基因组变异中 ,除了微卫星ＤＮＡ多态性外 ,最常见的一种形式为单核苷酸多态性 (ｓｉｎｇｌｅｎｕ ｃｌｅｏｔｉｄｅｐｏｌｙｍｏｒｐｈｉｓｍ ,ＳＮＰ) ,约占人类ＤＮＡ多态性的90 %以上。ＳＮＰ在群体遗传学、遗传性疾病、肿瘤和药物开发等研究中具…     

人类基因组单体型图在人类常见病相关性基因研究中的应用与展望

人类基因组单体型图是构建人类DNA序列中多态位点的常见模式图,其预期成果将成为人们确定对人类健康和疾病,以及对药物和环境反应有影响的相关基因的关键信息,并有助于加速相关诊断工具的开发.本文将就人类基因组单体型图在人类常见病相关性基因研究中的应用进行综述.     

模式动物斑马鱼在肾脏疾病研究中的应用

斑马鱼的肾单位结构、功能和分子组成与高等哺乳动物后肾高度保守,已广泛应用于肾脏领域的研究。本文将介绍斑马鱼肾脏的基本生物学特征,阐述斑马鱼在肾脏发育及多种肾脏疾病中的应用。斑马鱼模型适合于多重基因编辑及高通量基因功能筛查,在功能基因组学研究中极具前景。     

斑马鱼作为肝癌模型的应用进展

近年来,肝癌的发病率呈上升趋势,进一步了解肝癌发生的相关分子机制,了解其致病机理,对保障健康有重要意义。斑马鱼是一种重要的模式生物,与人类基因高度保守,其生长速度快,早期胚胎透明,有助于对发育过程实时观测;并且其肝脏细胞的构成、功能、信号通路,甚至是对于损伤的反应都与人类极度相似。在现代生物研究中,斑马鱼作为人类肝病模型得到广泛应用。主要介绍了斑马鱼作为肝癌模型的应用及研究进展,认为斑马鱼肝癌模型构建技术已经较为成熟,随着实验技术的不断发展,其在肝癌研究领域将取得更大的进步。     

维生素D缺乏与慢性肾脏病关系的研究进展

<正>维生素D是一种具有特殊的细胞溶质受体的脂溶性类固醇激素,参与调节人类基因组近3%的基因。维生素D最初被认为在钙、磷代谢中起着重要作用。近年来研究发现,维生素D缺乏与普通人群中的许多事件及疾病有关,如跌倒、骨折、DM、自身免疫性疾病、心血管和肾脏疾病、肺结核、抑郁症、神经退行性疾病和癌症[1]。目前,世界范围内慢性肾脏疾病     

生命科学信息化、系统化研究时代消化道肿瘤基础与临床研究的新思路

1953年4月,James Watson和Francis Crick在《Nature》上发表了著名的DNA双螺旋结构[1]。近50年以后的今天,人类基因组计划(Human GenomeProject)草图已完成并于2001年同时公布在《Nature》[2]和《Science》[3]上。人类基因组是现代人类赖以存在的遗传学蓝图,该计划对这一星球上每个人的生活都具有非同寻常的影响。这一科学上的重大突破在生命科学领域引起了轰动,喜悦和兴奋由此波及到其他研究领域并最后渗透到普通大众之中,C、A、G、T们的故事对于最大多数的读者而言变得有意义了。目前,人类基因组的30亿个碱基序列数据已经能在网上查询了。获得基因组序列仅仅是一个开始,科学家们更想知道的是基因及其在疾病预防、诊断和治疗中能起到的作用。当前研究的目的在于发现基因及其产物蛋白质的作用,以及它们如何影响人类的健康和疾病。大规模分析基因及其编码产物、被称作功能基因组学(functional genomics)的研究正悄然兴起。国际人类蛋白质组计划和国际人类基因组单体型图计划也分别于2001年和2003年正式启动。随着这些研究的不断深入,将会有大量新的重大发现,因此...     

斑马鱼模型和相关技术及其在内分泌系统的应用和前景

斑马鱼是一种热带淡水鱼,与其他动物模型相比在生物学、基因组学和遗传学方面有独特的优势.目前,在一些系统,如血液和神经系统,斑马鱼已经成为研究发育以及疾病非常有力的工具.随着斑马鱼模型的日渐成熟和相关研究技术的不断发展,其已逐步被应用于内分泌系统.本文主要对斑马鱼模型的优势、相关技术及其在内分泌领域取得的研究作简要综述.     

Fishing for gene function--endocrine modelling in the zebrafish

The use of zebrafish (Danio rerio) in scientific research is growing rapidly. It initially became popular as a model of vertebrate development because zebrafish embryos develop rapidly and are transparent. In the past 5 years, the sequencing of the zebrafish genome has increased the profile of zebrafish research even further, expanding into other areas such as pharmacology, cancer research and drug discovery. The use of zebrafish in endocrine research has mainly been confined to the study of the development of endocrine organs. However, it is likely to be a useful model in other areas of endocrinology, as there are a wide variety of both forward and reverse genetic techniques that can be employed in the zebrafish to decipher gene function in disease states. In this review, we compare the endocrine system of the zebrafish to mouse and human, demonstrating that the systems are sufficiently similar for zebrafish to be employed as a model for endocrine research. We subsequently review the repertoire of genetic techniques commonly employed in the zebrafish model to understand gene function in vertebrate development and disease. We anticipate that the use of these techniques will make the zebrafish a prominent model in endocrine research in the coming years.     

Comparative aspects of zebrafish (Danio rerio) as a model for aging research

The zebrafish has emerged over the past decade as a major model system for the study of development due to its invertebrate-like advantages coupled with its vertebrate biology. These features also make it a potentially valuable organism for gerontological research. The main advantages of zebrafish include its economical husbandry, small yet accessible size, high reproductive capacity, genetic tractability, and a large and growing biological database. Although zebrafish life span is longer than rodents, it shares the feasibility of large-scale mutational analysis with the extremely short-lived invertebrate models. This review compares zebrafish with the more widely used model organisms used for aging research, including yeast, worms, flies, mice, and humans.     

Zebrafish as a model to study cardiac development and human cardiac disease

Over the last decade, the zebrafish has entered the field of cardiovascular research as a new model organism. This is largely due to a number of highly successful small- and large-scale forward genetic screens, which have led to the identification of zebrafish mutants with cardiovascular defects. Genetic mapping and identification of the affected genes have resulted in novel insights into the molecular regulation of vertebrate cardiac development. More recently, the zebrafish has become an attractive model to study the effect of genetic variations identified in patients with cardiovascular defects by candidate gene or whole-genome-association studies. Thanks to an almost entirely sequenced genome and high conservation of gene function compared with humans, the zebrafish has proved highly informative to express and study human disease-related gene variants, providing novel insights into human cardiovascular disease mechanisms, and highlighting the suitability of the zebrafish as an excellent model to study human cardiovascular diseases. In this review, I discuss recent discoveries in the field of cardiac development and specific cases in which the zebrafish has been used to model human congenital and acquired cardiac diseases.     

Comparative aspects of zebrafish (Danio rerio) as a model for aging research

The zebrafish has emerged over the past decade as a major model system for the study of development due to its invertebrate-like advantages coupled with its vertebrate biology. These features also make it a potentially valuable organism for gerontological research. The main advantages of zebrafish include its economical husbandry, small yet accessible size, high reproductive capacity, genetic tractability, and a large and growing biological database. Although zebrafish life span is longer than rodents, it shares the feasibility of large-scale mutational analysis with the extremely short-lived invertebrate models. This review compares zebrafish with the more widely used model organisms used for aging research, including yeast, worms, flies, mice, and humans.     

Life spans and senescent phenotypes in two strains of Zebrafish (Danio rerio)

Zebrafish have become a widely used model organism in developmental biology research. In order to initiate an experimental foundation for aging studies, we have determined some basic gerontological parameters for populations of outbred zebrafish, and the golden sparse strain. Outbred zebrafish manifested a mean life span of about 42 months, with the longest living individual surviving for 66 months. The golden sparse populations had a mean life span of 36 months and a maximum longevity of 58 months. Skeletal length at death increased with age, suggestive of indeterminate growth. A common age-related phenotype was spinal curvature. Radiographic analysis excluded bony changes as the cause of the spinal curvature, suggesting muscle abnormalities as a primary mechanism. These data and a growing abundance of related biological resources suggest that the zebrafish may be a compelling model organism for studies on aging.     

Zebrafish and cardiac toxicology

Model systems are a mainstay in toxicological research. Zebrafish are rapidly becoming an important model organism for studying vertebrate development. The advantages of zebrafish: short reproductive cycle, production of numerous transparent, synchronously developing embryos, low cost, and standardization make zebrafish an attractive model for toxicologists as well. The use of these fish to study heart development has moved forward very rapidly, laying the groundwork for studying the effects of chemicals on cardiac development and function. Here we describe approaches that can be used to study cardiac toxicity in developing zebrafish, focusing on examples where zebrafish embryos have been especially useful in understanding the impact of specific toxicants on heart development and function.     

Differences in acute alcohol-induced behavioral responses among zebrafish populations

Background: With the arsenal of genetic tools available for zebrafish, this species has been successfully used to investigate the genetic aspects of human diseases from developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing as CNS disorders may be modeled and studied with this species. Alcoholism and alcohol abuse are among the most devastating and costliest diseases. However, the mechanisms of these diseases are not fully understood. Zebrafish has been proposed as a model organism to study such mechanisms. Characterization of alcohol’s effects on zebrafish is a necessary step in this research. Methods: Here, we compare the effects of acute alcohol (EtOH) administration on the behavior of zebrafish from 4 distinct laboratory‐bred populations using automated as well as observation based behavioral quantification methods. Results: Alcohol treatment resulted in significant dose‐dependent behavioral changes but the dose–response trajectories differed among zebrafish populations. Conclusions: The results demonstrate for the first time a genetic component in alcohol responses in adult zebrafish and also show the feasibility of high throughput behavioral screening. We discuss the exploration and exploitation of the genetic differences found.     

Molecular characterization of the GnRH system in zebrafish (Danio rerio): cloning of chicken GnRH-II,adult brain expression patterns and pituitary content of salmon GnRH and chicken GnRH-II

The zebrafish has proven to be a model system with unparalleled utility in vertebrate genetic and developmental studies. Substantially less attention has been paid to the potential role that zebrafish can play in answering important questions of vertebrate reproductive endocrinology. As an initial step towards exploiting the advantages that the zebrafish model offers, we have characterized their gonadotropin-releasing hormone (GnRH) system at the molecular level. GnRHs comprise a family of highly conserved decapeptide neurohormones widely recognized to orchestrate the hormonal control of reproduction in all vertebrates. We have isolated the gene and cDNA encoding chicken GnRH-II (cGnRH-II) from zebrafish, as well as several kilobases of upstream promoter sequence for this gene. As the gene encoding salmon GnRH (sGnRH) has been previously isolated (Torgersen et al, 2002), this is the second GnRH gene isolated from zebrafish to date. We have localized expression of these two genes in the brains of reproductively mature zebrafish using in situ hybridization. sGnRH is localized to the olfactory bulb-terminal nerve region (OB-TN), the ventral telencephalon-preoptic area (VT-POA) and, as we report here for the first time in any teleost species, the hindbrain. cGnRH-II is expressed exclusively in the midbrain, as has been found in all other jawed vertebrate species examined. Finally, the levels of both GnRH peptides in pituitaries of reproductively mature zebrafish were quantified using specific ELISAs. sGnRH pituitary peptide levels were shown to be 3- to 4-fold higher than cGnRH-II pituitary peptide. The cumulative results of these experiments allow us to conclude that zebrafish express just two forms of GnRH in a site-specific manner within the brain, and that sGnRH is the hypophysiotropic GnRH form. This work lays the foundation for further research into the control of reproduction in zebrafish, such as the functional significance of multiple GnRHs in vertebrates, and the molecular mechanisms controlling tissue-specific GnRH expression.     

Zebrafish facilitate non-alcoholic fatty liver disease research: Tools,models and applications

Non-alcoholic fatty liver disease (NAFLD) has become an increasingly epidemic metabolic disease worldwide. NAFLD can gradually deteriorate from simple liver steatosis, inflammation and fibrosis to liver cirrhosis and/or hepatocellular carcinoma. Zebrafish are vertebrate animal models that are genetically and metabolically conserved with mammals and have unique advantages such as high fecundity, rapid development ex utero and optical transparency. These features have rendered zebrafish an emerging model system for liver diseases and metabolic diseases favoured by many researchers in recent years. In the present review, we summarize a series of tools for zebrafish NAFLD research and the models established through different dietary feeding, hepatotoxic chemical treatments and genetic manipulations via transgenic or genome editing technologies. We also discuss how zebrafish models facilitate NAFLD studies by providing novel insights into NAFLD pathogenesis, toxicology research, and drug evaluation and discovery.     

Harnessing zebrafish for the study of white blood cell development and its perturbation

Considerable progress has been made in understanding the molecular basis of normal white blood cell development and its perturbation in disease through the use of clinical studies and traditional animal and cell line models. Despite this, however, many questions are still being answered and white blood cell disorders, including leukemia and lymphoma, remain a significant health problem. The zebrafish (Danio rerio) has emerged as a powerful alternative vertebrate model for the study of development and disease. We review the recent application of zebrafish to the study of white blood cell development and its disruption, particularly leukemogenesis. Such studies have highlighted the overall conservation of these processes throughout vertebrates, and establish zebrafish as a useful experimental model. This organism is now poised to make an important contribution to our understanding of the underlying genetic control of white blood cell development and its disruption, as well as the identification of new therapeutic agents.